Transcriptional Regulation of Steroidogenic‐Related Genes by SF‐1 Through its Dependent Alternations of Chromatin Structure

Steroidogenic factor 1 (SF‐1) is known as a transcription factor that plays a pivotal role in the regulation of reproductive endocrine functions at multiple levels during adrenal and gonadal development and differentiation. Recently, we found that SF‐1 induces the differentiation of mesenchymal stem cells (MSCs) into steroidogenic cells. To elucidate the molecular mechanisms of SF‐1‐mediated transcriptional activation in the differentiated MSCs, we carried out several experiments from both transcriptional and biochemical points of view. We identified novel distal control region upstream of the human Steroidogenic Acute Regulatory protein (StAR) gene, which is one of the SF‐1 target genes, and demonstrated that this region participate in StAR activation through SF‐1 dependent alterations of chromatin structure, including histone eviction and chromatin loop formation. Next, SF‐1 immune‐affinity chromatography followed by MALDI‐TOF MS analysis was performed to identify the nuclear complex components with SF‐1. More than twenty proteins were identified as the SF‐1 associated proteins including transcription factors, remodeling factors and DNA replication factors, etc. These proteins would work with SF‐1 to change in chromatin structure and enhance the transcriptional activity of the SF‐1 target genes.